Glycemic control, weight-loss effects, and safety of cotadutide in individuals with type 2 diabetes: A systematic review and meta-analysis

Table 2 Comparison of the safety outcomes in the cotadutide group vs the placebo control group

Outcome variables (categorical)	Cotadutide dose	Number of studies reporting the outcome	Number of participants with outcome/participants analyzed		Pooled effect size, RR (95%CI)	I2 (%)	P value
			Cotadutide	PCG
TEAEs	All doses	9	739/931	175/269	1.20 (1.07-1.35)	24	0.002
	100 μg/day	3	124/170	114/179	1.13 (0.99-1.29)	0	0.08
	200 μg/day	4	252/314	103/161	1.21 (0.98-1.49)	50	0.07
	300 μg/day	6	313/387	146/232	1.26 (1.12-1.41)	6	0.0001
	600 μg/day	2	50/60	40/55	1.46 (0.51-4.22)	50	0.48
TRAEs	All doses	5	418/697	57/185	1.96 (1.50-2.56)	26	< 0.00001
	200 μg/day	3	184/299	42/145	1.97 (1.21-3.20)	67	0.007
	300 μg/day	3	188/298	39/152	2.40 (1.82-3.15)	0	< 0.00001
Serious AEs	All doses	9	84/931	20/269	0.99 (0.62-1.58)	0	0.97
	100 μg/day	3	17/170	17/179	1.06 (0.56-2.00)	0	0.86
	200 μg/day	4	35/314	13/161	1.18 (0.65-2.14)	0	0.59
	300 μg/day	6	27/387	19/232	0.81 (0.46-1.43)	0	0.47
	600 μg/day	2	5/60	5/55	1.06 (0.33-3.44)	NA	0.92
Discontinuation of the study drug due to AEs	All doses	7	134/880	10/230	2.54 (1.39-4.64)	0	0.002
	100 μg/day	3	15/170	9/179	1.31 (0.22-7.83)	71	0.76
	200 μg/day	3	47/289	5/135	3.75 (1.65-8.56)	0	0.002
	300 μg/day	5	62/361	10/219	2.40 (0.92-6.29)	27	0.08
	600 μg/day	2	10/60	4/55	2.66 (0.89-7.90)	NA	0.08
Any GI AEs	All doses	4	380/675	47/155	1.86 (1.45-2.38)	0	< 0.00001
	200 μg/day	2	167/281	44/138	1.81 (1.25-2.60)	44	0.001
	300 μg/day	2	163/282	33/125	2.17 (1.60-2.96)	0	< 0.00001
Abdominal distension	All doses	5	10/264	0/133	2.73 (0.69-10.77)	0	0.15
	100 μg/day	2	1/67	0/67	2.94 (0.12-70.61)	NA	0.51
	200 μg/day	2	6/40	0/42	13.50 (0.80-227.75)	NA	0.07
	300 μg/day	4	3/106	0/107	2.76 (0.45-16.72)	0	0.27
Abdominal pain	All doses	7	11/308	4/153	1.18 (0.45-3.13)	0	0.73
	100 μg/day	2	0/67	1/67	0.33 (0.01-7.85)	NA	0.49
	200 μg/day	3	3/58	2/49	0.87 (0.16-4.92)	0	0.88
	300 μg/day	5	6/132	2/120	1.67 (0.49-5.71)	0	0.42
Dyspepsia	All doses	8	82/886	6/253	3.46 (1.71-7.02)	0	0.0006
	100 μg/day	2	8/155	2/163	3.67 (0.91-14.77)	0	0.07
	200 μg/day	3	27/299	3/145	4.22 (1.41-12.63)	0	0.01
	300 μg/day	5	46/372	5/216	4.07 (1.81-9.15)	0	0.0007
	600 μg/day	2	1/60	0/55	1.15 (0.06-23.88)	NA	0.93
GERD	All doses	6	9/282	0/140	2.12 (0.46-9.78)	0	0.33
	100 μg/day	2	1/67	0/67	2.94 (0.12-70.61)	NA	0.51
	200 μg/day	3	1/58	0/49	1.26 (0.06-27.82)	NA	0.88
	300 μg/day	4	4/106	0/107	3.66 (0.61-21.81)	0	0.15
Nausea	All doses	9	312/931	28/269	3.13 (2.21-4.45)	0	< 0.00001
	100 μg/day	3	31/170	15/179	2.22 (1.25-3.95)	0	0.007
	200 μg/day	4	118/314	20/161	3.05 (1.98-4.68)	0	< 0.00001
	300 μg/day	6	142/387	21/232	3.47 (2.29-5.27)	0	< 0.00001
	600 μg/day	2	21/60	2/55	6.82 (1.93-24.13)	0	0.003
Vomiting	All doses	9	154/931	9/269	3.84 (2.13-6.91)	0	< 0.00001
	100 μg/day	3	15/170	6/179	2.45 (0.99-6.05)	0	0.05
	200 μg/day	4	68/314	6/161	4.55 (2.14-9.68)	0	< 0.0001
	300 μg/day	6	63/387	8/232	3.88 (2.00-7.55)	0	< 0.0001
	600 μg/day	2	8/60	1/55	4.13 (0.75-22.66)	0	0.10
Eructation	All doses	6	39/854	2/229	2.74 (0.89-8.41)	0	0.08
	100 μg/day	2	2/152	1/163	1.41 (0.09-22.80)	38	0.81
	200 μg/day	3	21/299	1/145	5.13 (1.20-21.99)	0	0.03
	300 μg/day	4	16/352	1/196	2.79 (0.62-12.48)	0	0.18
Constipation	All doses	8	55/914	7/249	2.26 (1.16-4.40)	0	0.02
	100 μg/day	3	4/170	4/179	0.99 (0.26-3.83)	0	0.99
	200 μg/day	4	19/314	5/161	2.20 (0.88-5.51)	0	0.09
	300 μg/day	5	24/366	4/212	2.74 (1.06 -7.13)	0	0.04
	600 μg/day	2	8/64	2/55	2.25 (0.55-9.27)	0	0.26
Diarrhea	All doses	8	117/905	22/256	1.16 (0.61-2.19)	26	0.65
	100 μg/day	3	18/170	12/179	1.58 (0.79-3.14)	0	0.19
	200 μg/day	4	57/314	17/161	1.14 (0.38-3.39)	64	0.81
	300 μg/day	5	38/361	15/219	1.37 (0.65-2.86)	11	0.41
	600 μg/day	2	4/60	2/55	1.47 (0.32-6.67)	0	0.62
Flatulence	All doses	5	9/242	2/117	1.49 (0.43-5.18)	0	0.53
	200 μg/day	2	1/43	1/33	0.67 (0.07-6.10)	0	0.72
	300 μg/day	3	5/96	1/84	2.45 (0.50-12.08)	0	0.27
Decreased appetite	All doses	8	70/919	5/265	3.81 (1.80-8.06)	0	0.0005
	100 μg/day	3	3/170	2/179	1.34 (0.14-13.05)	31	0.80
	200 μg/day	4	25/314	1/161	6.39 (1.79-22.84)	0	0.004
	300 μg/day	6	37/387	5/232	3.57 (1.56-8.20)	0	0.003
Fatigue	All doses	4	19/224	4/110	2.34 (0.92-5.95)	0	0.07
	300 μg/day	3	10/96	4/84	1.72 (0.58-5.15)	4	0.33
Dizziness	All doses	8	51/920	11/265	1.51 (0.80-2.87)	0	0.20
	100 μg/day	3	5/167	4/179	1.36 (0.37-4.98)	0	0.64
	200 μg/day	4	17/314	8/161	1.19 (0.52-2.74)	0	0.68
	300 μg/day	6	27/388	6/232	2.40 (1.07-5.37)	0	0.03
Headache	All doses	8	64/887	14/253	1.59 (0.91-2.77)	0	0.11
	100 μg/day	2	4/152	4/163	1.08 (0.28-4.25)	0	0.91
	200 μg/day	3	26/299	7/145	1.75 (0.48-6.33)	58	0.40
	300 μg/day	5	30/373	10/216	1.60 (0.81-3.17)	0	0.18
	600 μg/day	2	4/63	1/55	2.14 (0.36-12.92)	0	0.41
Hypoglycemia	All doses	4	35/223	11/110	1.16 (0.64-2.09)	0	0.63
	300 μg/day	3	13/95	11/84	1.11 (0.53-2.33)	0	0.77

TEAE: Treatment-emergent adverse events; TRAE: Treatment-related adverse events; AE: Adverse events; GI: Gastrointestinal; GERD: Gastroesophageal reflux disease; PCG: Placebo control group; NA: Not applicable; RR: Risk ratio; CI: Confidence interval.